RU2632768C1 - Differential diagnostic technique for hepatic growths during ultrasound examination - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention can be used for the differential diagnostic of tumour growths in the liver. An ultrasound examination is performed in the fasted state on the scanner, which provides the possibility of carrying out shear wave elastometry. After the detection of liver parenchyma areas with the presence of focal lesions, the area of growth is enclosed in the survey window. The parameters of the shear wave elastometry mode are optimized. At least tenfold determination of the shear wave velocity (m/s) in the lesion is carried out and its minimum (N_min) and maximum (N_max) values are determined. The area of the unchanged liver parenchyma is enclosed in the survey window, at least tenfold determination of the shear wave velocity (m / s) in the unchanged parenchyma is carried out and it minimum (P_min) and maximum (P_max) values are determined. All these values are substituted into each of the four formulas for calculating the classification functions (CF): I) CF-I = 15.332× N_max + 1.635 × N_min + 46.502 × P_max + 11.410 × P_min - 76.784; II) CF-II = 11.940 × N_max + 15.743 × N_min + 38.718 × P_max + 49.926 × P_min - 125.872; III) CF-III = 9.897 × N_max + 7.348 × N_min + 47.042 × P_max + 45.784 × P_min - 110.752; IV) CF-IV = 15.731 × N_max + 19.743 × N_min + 35.605 × P_max + 29.361 × p_min - 117.041. It is determined which of the four classification functions will have the maximum value in the series of obtained values. At the maximum value of CF-I, the patient is diagnosed with hepatic haemangioma. In the case of a maximum value of CF-II, the patient is diagnosed with hepatocellular adenoma. At the maximum value of CF-III, the patient is diagnosed with hepatocellular carcinoma. At the maximum value of CP-IV, the patient is diagnosed with colorectal cancer metastasis.

EFFECT: method provides high quality of differential diagnosis of malignant and benign liver growths, reduces the number of diagnostic errors.

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Description

The present invention relates to medicine and can be used in ultrasound diagnostics in order to differentiate benign and malignant neoplasms of the liver of various origins.

The relevance of the prospects for the differential diagnosis of malignant and benign neoplasms of internal organs, including the liver, when using the ultrasonic research method is not in doubt, given its non-invasive nature and the absence of radiation exposure. At present, in our country, mortality from liver cancer is 1.5% of all cases of cancer deaths, but in developed countries it is in third place in the case of mortality from cancer, fluctuating around 9%. [Schukina O.E. The informational content of the ultrasound method in the diagnosis of liver cancer / Bulletin of medical Internet conferences. - 2013. Volume 3. No. 2. - S. 205]. However, in developing countries, according to WHO, the incidence of liver cancer among oncological diseases is up to 77% of all cases [Cancer incidence statistics / http://www.knigamedika.ru/novoobrazovaniya-onkologiya/statistika-zabolevaemosti-rakom.html].

The effectiveness of the application of radiation (ultrasound, computed, magnetic resonance and positron emission tomography, static scintigraphy) and instrumental methods of research (celiacography, percutaneous puncture biopsy, laparoscopy) strongly depends on the size of the neoplasm nodes in the liver and calculi in the ducts of the hepatobiliary system. When the size of calculi is from 2 to 4 mm in the bile ducts, their detection is impossible either using conventional transabdominal ultrasound, or by methods of magnetic resonance cholangiopancreatography [Boboev B. D., Morozov V. P. The use of modern radiation research methods in the diagnosis of choledocholithiasis / Scientific notes of St. Petersburg State Medical University. Acad. I.P. Pavlova. 2010.T. XVII. No. 2. S. 62-65]. The lack of reliable diagnostic tools does not allow reliable verification of the presence of focal liver lesions with a diameter of less than 5 mm, which, in turn, prevents the timely appointment of adequate treatment for a particular patient.

- 2011. - Т. 157, №6 - С. 61-70.]. Кроме того, минимальный размер узла при проведении пункционной биопсии под контролем эхографии, по мнению ряда авторов, не может быть меньше 5 мм [Mikosch P., Gallowitsch Н.J., Kresnik Е. et al. Value of ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in an endemic goitre area / Eur. J. Nucl. Med. - 2000. - 27, №1. - P. 62-69].An analogue of the proposed method for the differential diagnosis of benign and malignant liver tumors is a percutaneous puncture biopsy of the liver followed by histopathological and / or cytological examination of the biopsy. The disadvantages of the method are: the invasive nature of the procedure, the probable errors of taking the material from the pathological focus, associated with the level of training of the personnel performing the procedure, as well as the qualification of the pathologist / cytologist [Matyaschuk SI, Naida Yu.N., Shelkova EA Indications for puncture biopsy (TAPB) of thyroid glands Lyki

- 2011. - T. 157, No. 6 - S. 61-70.]. In addition, the minimum node size during a puncture biopsy under the control of ultrasound, according to some authors, cannot be less than 5 mm [Mikosch P., Gallowitsch N.J., Kresnik E. et al. Value of ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in an endemic goitre area / Eur. J. Nucl. Med. - 2000. - 27, No. 1. - P. 62-69].

The closest analogue of the proposed method for differential diagnosis of benign and malignant tumors of the liver can be considered a method of transabdominal ultrasound using color Doppler mapping [Schukina O.E. Informational content of the ultrasound method in the diagnosis of liver cancer / Bulletin of medical Internet conferences - 2013. Volume 3. No. 2. - S. 205], which allows to reach the level of diagnostic sensitivity of 85% and diagnostic specificity of 72%. The disadvantage of this method can be considered relatively low values of diagnostic sensitivity and specificity. When using this method, it will not be verified in 15% of patients with a malignant neoplasm, and in 28% without a malignant process, it will be diagnosed.

The objectives of the proposed method are to provide reliable differential diagnosis of malignant and benign nature of tumors in the liver, reducing the frequency of diagnostic errors, improving the quality of treatment of patients with liver tumors.

The essence of the invention lies in the fact that for the differential diagnosis of neoplasms in the liver of a patient, a percutaneous ultrasound scan is performed on an empty stomach using the method of shear wave elastometry on an ultrasound scanner and. after detecting areas of the liver parenchyma with the presence of focal formations, the neoplasm is enclosed in a polling window, the shear wave elastometry mode parameters are optimized, and then shear wave velocity is determined at least ten times in the neoplasm and find its minimum (N _min ) and maximum (N _{min max)} value, and then enclosed in a box plot survey unaltered liver parenchyma and performed by at least tenfold determination of shear wave velocity in the unmodified parenchyma find it min is minimum (P _min) and maximum (P _max) value, and then determine the values of classification functions (KF):

I) CF-I = 15,332 × N _max + 1,635 × N _min + 46,502 × P _max + 11,410 × P _min - 76,784;

II) CF-II = 11.940 × N _max + 15.743 × N _min + 38.718 × P _max + 49.926 × P _min - 125.872;

III) CF-III = 9.897 × N _max + 7.348 × N _min + 47.042 × P _max + 45.784 × P _min - 110.752;

IV) CF-IV = 15.731 × N _max + 19.743 × N _min + 35.605 × P _max + 29.361 × P _min - 117.041,

and with a maximum value of CF-I in a series of CF values, the patient is diagnosed with liver hemangioma, in the case of a maximum value of CF-II, the patient is diagnosed with hepatocellular adenoma, with a maximum value of CF-III, the patient is diagnosed with hepatocellular carcinoma, and with a maximum value of CF-IV the patient is diagnosed with metastasis of colorectal cancer.

The method is carried out as follows: a patient is performed on an empty stomach strictly percutaneously by ultrasound on an ultrasound scanner that allows shear wave elastometry (a possible but not the only device is Aixplorer by SuperSonic Imagine (France) using a 1-6 MHz convex sensor , “Liver” preset) and, after detecting areas of the liver parenchyma with the presence of focal formations, the neoplasm is enclosed in a polling window, the shear wave elastometry mode parameters are optimized, and then m carry out a tenfold measurement of the velocity of a shear wave, depending on the stiffness of the tissue. Then, the minimum and maximum values of the shear wave velocity are determined. Similarly, the shear wave velocity in the “unchanged” liver parenchyma outside the focal formation is measured in the same number of repetitions, also determining its minimum and maximum values. The values determined during the study of the patient: the maximum value of the shear wave velocity in the tumor site (N _max ), the minimum value of the shear wave velocity in the tumor site (N _min ), the maximum value of the shear wave velocity in the liver parenchyma outside the focal formation (P _max ) and the minimum shear wave velocity in the liver parenchyma outside the focal formation (P _min ) - is substituted into each of the four formulas for calculating the classification functions (CF) I ÷ IV: _

I) CF-I = 15,332 × N _max + 1,635 × N _min + 46,502 × P _max + 11,410 × P _min - 76,784;

II) CF-II = 11.940 × N _max + 15.743 × N _min + 38.718 × P _max + 49.926 × P _min - 125.872;

III) CF-III = 9.897 × N _max + 7.348 × N _min + 47.042 × P _max + 45.784 × P _min - 110.752;

IV) CF-IV = 15.731 × N _max + 19.743 × N _min + 35.605 × P _max + 29.361 × P _min - 117.041, calculating the values of all four classification functions for a particular patient. Depending on which of the CFs will be of maximum value, the question of what kind of a detected neoplasm has is resolved. If the largest value of the compared four CFs will have CF-I, then the patient is diagnosed with hemangioma of the liver. If CF-II will be of the greatest importance, then the patient has a liver adenoma (benign disease). If CF-III is of greatest importance, then the patient is diagnosed with hepatocellular carcinoma, and with the highest value of CF-IV, the patient is diagnosed with colorectal cancer metastasis.

As a result of the study, an independent sample of 46 patients showed that for groups of patients with hemangiomas and metastases of colorectal cancer, one hundred percent diagnostic sensitivity and specificity were achieved. In groups with liver adenoma and with hepatocellular carcinoma, the correctness of assignment to the group was 90%. In one patient with liver adenoma, hepatocellular adenoma was diagnosed by this method, and, conversely, in one patient with hepatocellular carcinoma, liver adenoma was erroneously diagnosed. Thus, the probability of the correct determination of the differential diagnosis for liver tumors was 95.6%.

The technical result. This method allows high-precision differential diagnosis of liver tumors, thereby reducing the frequency of diagnostic errors and, consequently, improving the quality of treatment of patients with liver tumors due to a comprehensive assessment of the maximum and minimum values of shear wave velocity at the same time in the lesion focus and in the parenchyma liver, not affected by the pathological process.

Example 1. Patient R., 48 years old. Complaints of general weakness, discomfort, drawing pain and a feeling of fullness in the right side, worse after eating. The abdomen on palpation is moderately painful in the right hypochondrium. The patient considers himself about two months when for the first time after eating fatty foods she felt nauseous and aching pain in the right hypochondrium.

From laboratory data: moderate thrombocytopenia (135 × 10 ⁹ / L) was determined in a clinical blood test.

Ultrasound on an empty stomach in a patient in B-mode: in the region of the right lobe of the liver, a 10 × 6 × 4 cm formation was visualized, occupying the V and VI segments of the liver. The formation has fuzzy, uneven contours and a hypoechoic, somewhat heterogeneous internal structure. During a Doppler study in the energy mapping mode, diffuse, mainly venous blood flow is determined.

In the shear wave elastometry mode in tenfold repetition, the shear wave velocity in the foci of neoplasms N _max = 3.81 m / s and N _min = 0.98 m / s, as well as in the unchanged liver parenchyma P _max = 1.86 m / s and P _min = 0.54 m / s.

When substituting these values in the formulas for calculating CF (I ÷ IV), the following values were obtained: CF-I = 75.89, CF-II = 34.02; CF-III = 46.38; CF-IV = 44.32. Since CF-I is of maximum importance, it is concluded that the patient has liver hemangioma and, accordingly, the benign nature of the neoplasm.

According to x-ray computed tomography, the liver is enlarged, signs of portal and biliary hypertension are not detected. In the right lobe of the liver, in the region of segments V and VI, a volume formation of 100 × 61 × 43 mm in size, nonuniformly reduced density (32-38 HU), with uneven, clear contours was revealed.

X-ray computed tomography with contrast showed an uneven accumulation of contrast by formation with an increase in density along the periphery in the arterial phase and in the center in the venous and parenchymal phases (symptom of the optical diaphragm). In the center of formation, a region of uniformly low density of 15-30 HU, with clear contours (hyaline gap), is defined. In the delayed phase, the formation continues to unevenly accumulate contrast medium.

A comprehensive radiological study made it possible to verify the diagnosis of cavernous hemangioma of the right lobe of the liver in this patient and confirm the diagnostic conclusion made by the proposed method.

Example 2. Patient S., age 15 years old, was admitted with complaints of general weakness, excessive sweating, dizziness, abdominal pain, nausea, vomiting, frequent loose stools up to 4–5 times a day. The duration of the disease is about two weeks.

According to the results of a laboratory examination in a clinical blood test, there is hypochromic iron deficiency anemia, neutropenia. According to the biochemical analysis of blood - a syndrome of cytolysis and cholestasis: an increase in ALT activity to 125 IU / L, ACT to 140 IU / L, alkaline phosphatase to 390 U / L (age norm 51-332 U / L).

An ultrasound examination of the abdominal organs on an empty stomach in a patient in B-mode revealed an increase in liver size (thickness of the right lobe - 159 mm, left - 98 mm). In the parenchyma, multiple round-shaped heterogeneous heterogeneous hyper- and isoechoic formations with clear even contours are visualized, maximum size 47 × 32 mm, minimum size 18 × 16 mm. In color Doppler mapping, all formations are hypervascular.

In the shear wave elastometry mode in tenfold repetition, the shear wave velocity in the foci of neoplasms N _max = 3.83 m / s and N _min = 3.09 m / s, as well as in the unchanged liver parenchyma P _max = 1.95 m / s and P _min = 1.69 m / s.

When substituting these values in the formulas for calculating CF (I ÷ IV), the following values were obtained: CF-I = 96.94, CF-II = 128.22; CF-III = 118.89; CF-IV = 123.07. Since CF-II is of maximum importance, it is concluded that the patient has hepatocellular adenoma and, accordingly, the benign nature of the neoplasm.

To confirm the conclusion, we determined the content of tumor markers in the blood serum. The concentration of α-fetoprotein (1.12 IU / ml) and cancer embryonic antigen (1.04 ng / ml) did not exceed normal values. A diagnostic puncture biopsy of the liver was also performed, which confirmed the diagnosis of multiple hepatocellular adenomas. Thus, the study of the level of tumor markers and histopathological examination allowed to confirm the diagnostic conclusion made by the proposed method.

Example 3. Patient S., age 62 years. Since 2003, he was registered in the dispensary with a diagnosis of chronic hepatitis C. He underwent ultrasound of the liver regularly. Last visit in 2013, in conclusion only diffuse changes in the liver were made. The last few months, the patient felt a deterioration in general condition in the form of general weakness, lack of appetite, nausea, vomiting, bloating, alternating constipation with diarrhea. Over the past month, the patient lost 5 kg in weight.

According to the result of a clinical blood test: hemoglobin - 85 g / l, white blood cells - 30 thousand. Biochemical blood test: ALT - 98.7 mmol / l, ACT - 129 mmol / l, lactate dehydrogenase - 381.2 u / l, alkaline phosphatase - 508.3 U / L, total bilirubin - 50.6 μmol / L, gamma-glutamyl transpeptidase - 192.6 U / L.

According to fasting ultrasound in a patient in B-mode: a volumetric formation was revealed in the right lobe of the liver up to 12 cm in size, mainly of hyperechoic echostructure, with uneven but relatively clear contours.

According to shear wave ultrasound elastometry: the liver is enlarged due to volume formation in the right lobe, its contour is uneven. In the VI segment of the right lobe of the liver, a volumetric formation was determined. A qualitative assessment of the formation showed a red pattern along the periphery of the formation and a blue-blue spectrum of staining in the central part of the formation. A quantitative assessment in shear wave elastometry in tenfold repetition measured the shear wave velocity in the foci of neoplasms N _max = 2.32 m / s and N _min = 1.47 m / s, as well as in the unchanged liver parenchyma P _max = 2, 89 m / s and P _min = 1.45 m / s.

When substituting these values in the formulas for calculating CF (MV), the following values were obtained: CF-I = 112.13, CF-II = 109.26; CF-III = 125.35; CF-IV = 93.95. Since CF-III is of maximum importance, it is concluded that the patient has hepatocellular carcinoma and, accordingly, the malignant nature of the neoplasm.

An additional computed tomographic study without contrast in the right lobe of the liver identified hypo-intensive education with sizes up to 12 cm, with a clear outline. The absorption coefficient of the internal structure of the tumor is 30-35 units. Hu. In the arterial phase of contrast enhancement, an uneven, but intense staining of the tumor was noted, in the portal phase, the tumor is hyperactive in comparison with the parenchyma containing the contrast agent.

Immunochemical study of the content of tumor markers in the peripheral blood: carbohydrate antigen (CA 19-9) - 77.6 U / ml (2 times excess), cancer embryonic antigen (CEA) - 14.3 ng / ml (3 ÷ 6 times excess) , alpha fetoproteins (AFP) - 43.5 U / ml (an excess of 5.5 times).

Conclusion: a tumor in the right lobe of the liver is the primary tumor of the liver (hepatocellular cancer).

Subsequently, the patient underwent right-sided hemihepatectomy, cholecystectomy.

A histopathological examination of the surgical material made it possible to determine a massive tumor node in the thickness of the liver with fairly clear boundaries of 12.5 × 9.0 × 13.0 cm; outside the tumor, the liver tissue is flabby, brown, and homogeneous. In the liver tissue, the tumor node has the structure of hepatocellular low-grade cancer. In the tumor, lymphoid infiltration is expressed, inflammatory infiltration is practically not expressed, necrosis is absent. There were no significant signs of vascular invasion. Outside the tumor in the liver tissue - Metavir F0 fibrosis level, 0 stage Knodell, 0 stage Ishak; the phenomena of severe chronic inflammatory infiltration of the portal tracts, with no signs of activity. Lymph nodes with mixed hyperplasia, without tumor growth.

Final histopathological diagnosis: hepatocellular cancer, T1N0M0. Stage of the tumor process: 1. As a result, we can conclude that the study of the level of tumor markers, a comprehensive x-ray examination and histopathological examination of the surgical biopsy specimen confirmed the diagnostic conclusion made by the proposed method.

Example 4. Patient M., 57 years old, was hospitalized in the surgical department with a diagnosis of Colorectal cancer T2N0M0, stage of the tumor process 2, condition after combined treatment. The patient underwent surgery - total mesorectumectomy, anterior resection. 6 months after the operation, with a control ultrasound of the abdominal organs in both lobes of the liver, hypoechoic rounded formations with a diameter of up to 3 cm with uneven and fuzzy contours, without peripherally changed tissues, were revealed.

Color and energy dopplerography showed the presence of peripheral blood flow, but the intratumoral vascularization could not be clearly identified.

An ultrasound examination of the abdominal organs on an empty stomach in a patient in B-mode, the liver is not enlarged (oblique vertical size of the right lobe = 15.1 cm), however, it has a tuberous contour. In the II segment, the subcapsular focus is 2.5 × 1.9 cm in size, in the VI segment, the subcapsular focus (on the visceral surface) is 3.1 × 3.0 cm, in the V segment is the subcapsular focus 3.1 × 2.1 cm. segments of the liver focal changes were not detected.

In shear wave elastometry in tenfold repetition, the shear wave velocity was measured in the foci of neoplasms N _max = 4.32 m / s and N _min = 3.47 m / s, as well as in the unchanged liver parenchyma P _max = 1.47 m / s and P _min = 1.15 m / s. When substituting these values in the formulas for calculating CF (MV), the following values were obtained: CF-I = 76.60, CF-II = 94.67; CF-III = 79.30; CF-IV = 105.53. Since CF-IV is of maximum importance and, taking into account the anamnesis, it is concluded that the patient has colorectal cancer metastases.

To verify the conclusion, a computed tomographic study was performed without contrast. According to its results, three hypo-intensive formations were found in both lobes of the liver parenchyma. In the II segment, the subcapsular focus is 2.5 × 1.9 cm in size, in the VI segment, the subcapsular focus (on the visceral surface) is 3.1 × 3.0 cm, in the V segment is the subcapsular focus is 3.1 × 2.1 cm. Densitometric profile each of the formations represents the lowest values of the absorption coefficient in the center of the node (15-20 HU), corresponding to the emerging tissue necrosis. In the direction from the center to the periphery of each focus, densitometric indices gradually increase and turn into the values of unchanged liver parenchyma. The boundaries of the tumor cannot be clearly differentiated.

Computed tomography with contrast (omniscan): in both lobes of the liver, hypovascular focal lesions were identified that are best seen in the portal vein phase.

Thus, a comprehensive x-ray study allowed us to verify the diagnosis obtained by the proposed method and to detect metastases of colorectal cancer in the liver.

An analysis of the above examples allows us to conclude that the determination of the maximum and minimum shear wave velocity in the tumor focus and in the unchanged liver parenchyma allows differential diagnosis of malignant and benign tumors of this organ.

Claims (6)

A method for the differential diagnosis of liver neoplasms, including an ultrasound performed on an empty stomach, using the shear wave elastometry method on an ultrasound scanner, characterized in that, after detecting areas of the liver parenchyma with the presence of focal formations, the neoplasm is enclosed in a survey window, the parameters of the elastometry mode are optimized shear wave, and then conduct at least ten-fold determination of the shear wave velocity in the tumor focus and find it mi the minimum (N _min ) and maximum (N _max ) values, then enclose a portion of the unchanged liver parenchyma in the polling window and determine at least ten times the shear wave velocity in the unchanged parenchyma, find its minimum (P _min ) and maximum (P _max ) values , after which the values of the classification functions (CF) are determined: I) CF-I = 15,332 × N _max + 1,635 × N _min + 46,502 × P _max + 11,410 × P _min -76,784; II) CF-II = 11.940 × N _max + 15.743 × N _min + 38.718 × P _max + 49.926 × P _min -125.872; III) CF-III = 9.897 × N _max + 7.348 × N _min + 47.042 × P _max + 45.784 × P _min -110.752; IV) CF-IV = 15.731 × N _max + 19.743 × N _min + 35.605 × P _max + 29.361 × P _min -117.041, and with a maximum value of CF-I in a series of CF values, the patient is diagnosed with liver hemangioma, in the case of a maximum value of CF-II, the patient is diagnosed with hepatocellular adenoma, with a maximum value of CF-III, the patient is diagnosed with hepatocellular carcinoma, and with a maximum value of CF-IV the patient is diagnosed with metastasis of colorectal cancer.